This proposal provides a plan for determination of the antigens, which are most important for tumor rejection in vivo in a rat colonic adenocarcinoma model with special emphasis on analysis of the embryonal antigens shown to be associated with these tumors. Various techniques to augment the immunogenicity of embryonal and carcinoma antigens and to modify the host immune response to increased CMI and decreased blocking activity will be studied. Sequential studies will be performed on rats with primary large bowel carcinomas and isografts such tumors. Correlations of the effect on tumor growth, as demonstrated by an established double contrast technique, and on various immune parameters including tumor specific CMI, serum blocking, and various antibody activities, by immune manipulations involving treatment with cyclophosphamide and 5-FU combined with lymphocyte transfers, administration of "unblocking antisera and treatment with modified carcinoma cells with or without immunostimulators will be analyzed. Rats and human patients with benign and premalignant lesions of the large bowel will be analyzed to determine their immune status with regard to adenocarcinoma cell antigens. The effect of conventional therapy, particularly chemotherapy, on the antitumor immune parameters are to be analyzed to obtain basic information for later application of immunotherapeutical procedures worked out in the rat model.